Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus.
Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus.
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脑水肿减轻有利于癫痫持续状态后类淋巴系统功能的恢复
DOI：
10.1172/jci.insight.151835
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发表时间：
2021-09-08
期刊：
影响因子：
8
通讯作者：
Huang K
中科院分区：
文献类型：
--
作者：
Liu K;Zhu J;Chang Y;Lin Z;Shi Z;Li X;Chen X;Lin C;Pan S;Huang K
癫痫持续状态(SE)是一种神经急症，常伴有急性脑水肿和长期认知损害，以神经变性和异常的过度磷酸化tau蛋白(p-tau)聚集为特征。胶质淋巴系统在促进代谢废物从脑中清除中起着中心作用，但它与SE后脑水肿和认知功能障碍的关系尚不清楚。我们推测SE后的脑水肿可能通过压迫损害淋巴系统的功能，从而导致代谢废物的清除障碍，最终影响长期认知功能。我们的结果表明，淋巴系统功能暂时受损，如双光子成像、MRI增强、脑切片成像和星形细胞水通道水通道蛋白4(AQP4)蛋白极化。MRI上脑水肿的严重程度与SE后8d内的淋巴系统功能障碍密切相关。此外，当用格列本脲治疗或Trpm4基因缺失减轻脑水肿时，SE后的淋巴系统功能恢复得更早，p-tau沉积的神经元减少，神经元变性，认知功能改善。这些结果表明，SE诱导的脑水肿可能导致淋巴系统功能障碍，并使SE后的大脑更容易出现p-tau聚集和神经认知功能障碍。
Status epilepticus (SE) is a neurological emergency usually accompanied by acute cerebral edema and long-term cognitive impairment, and is characterized by neurodegeneration and aberrant hyperphosphorylated tau protein (p-tau) aggregation. The glia-lymphatic (glymphatic) system plays a central role in facilitating the clearance of metabolic waste from the brain, but its relationship with cerebral edema and cognitive dysfunction after SE is unclear. We hypothesized that cerebral edema after SE might impair glymphatic system function through compression, thus leading to impaired removal of metabolic waste, and ultimately affecting long-term cognitive function. Our results showed that glymphatic system function was temporarily impaired, as evidenced by 2-photon imaging, MRI enhancement, imaging of brain sections, and astrocytic water channel aquaporin 4 (AQP4) protein polarization. The severity of cerebral edema on MRI correlated well with glymphatic system dysfunction within 8 days following SE. Moreover, when cerebral edema was alleviated by glibenclamide treatment or genetic deletion of Trpm4, post-SE glymphatic system function recovered earlier, along with fewer p-tau–deposited neurons and neuronal degeneration and better cognitive function. These findings suggest that SE-induced cerebral edema may cause glymphatic system dysfunction and render the post-SE brain vulnerable to p-tau aggregation and neurocognitive impairment.
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影响因子：
4.8
作者：
Alves, Marianna;Kenny, Aidan;Engel, Tobias
通讯作者：
Engel, Tobias
DOI：
10.1073/pnas.1110655108
发表时间：
2011-10-25
影响因子：
11.1
作者：
Haj-Yasein, Nadia Nabil;Vindedal, Gry Fluge;Nagelhus, Erlend Arnulf
通讯作者：
Nagelhus, Erlend Arnulf
影响因子：
17.1
作者：
Iliff JJ;Wang M;Liao Y;Plogg BA;Peng W;Gundersen GA;Benveniste H;Vates GE;Deane R;Goldman SA;Nagelhus EA;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
3.4
作者：
Bankstahl M;Breuer H;Leiter I;Märkel M;Bascuñana P;Michalski D;Bengel FM;Löscher W;Meier M;Bankstahl JP;Härtig W
通讯作者：
Härtig W
影响因子：
3
作者：
Marchi N;Banjara M;Janigro D
通讯作者：
Janigro D